{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:37:50Z","timestamp":1747802270396,"version":"3.41.0"},"reference-count":32,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation\n                        of China","doi-asserted-by":"crossref","award":["81100578"],"award-info":[{"award-number":["81100578"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013286","name":"Specialized Research Fund for the\n                        Doctoral Program of Higher Education of China","doi-asserted-by":"crossref","award":["20113234120011"],"award-info":[{"award-number":["20113234120011"]}],"id":[{"id":"10.13039\/501100013286","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Limited research has explored the efficacy of \u03b2-blockers in combination with\n                        unilateral total, subtotal, or partial adrenalectomy in ARMC5-mutated\n                        patients with primary bilateral macronodular adrenocortical hyperplasia\n                        (PBMAH). Additionally, there is no consensus on determining the optimal side\n                        for adrenal gland resection.<\/jats:p><jats:p> To assess the clinical utility of three unilateral adrenalectomy (ULA)\n                        modalities\u2014total, subtotal, and partial\u2014combined with \u03b2-blocker treatment in\n                        patients with PBMAH and Cushing\u2019s syndrome (CS). <\/jats:p><jats:p>This study was conducted at a single tertiary referral center involving a\n                        series of four patients with suspected CS. Diagnosis of PBMAH was confirmed\n                        through dexamethasone suppression testing, evaluation of ectopic receptor\n                        expression, and whole-exome sequencing. Three patients underwent unilateral\n                        total, subtotal, or partial adrenalectomy, respectively, while one patient\n                        declined surgery. All patients received \u03b2-blocker treatment. <\/jats:p><jats:p>The median treatment duration among the four ARMC5-mutuated PBMAH patients\n                        was 30.5 months (range: 6\u201345 months). Two patients who underwent total or\n                        subtotal adrenalectomy on the side with more pronounced nodularity showed\n                        postoperative improvement in clinical CS signs, glycemic control, and\n                        hypertension. These two patients, along with another patient with bilateral\n                        diffuse (non-nodular) adrenal hyperplasia who declined surgery, showed\n                        further improvement in hypercortisolism and cortisol\/adrenocorticotropic\n                        hormone (ACTH) ratio (CAR: plasma cortisol (nmol\/L)\/plasma ACTH (pg\/ml),\n                        newly reported as a reliable parameter of cortisol secretory capacity in\n                        patients with adrenal CS) after propranolol treatment. The patient who\n                        underwent partial adrenalectomy on the side with less pronounced nodularity\n                        showed no significant improvement in hypercortisolism or CAR, and the\n                        response to propranolol was also unsatisfactory. All four cases harbored\n                        pathogenic variants in the ARMC gene, including two novel germline\n                        mutations.<\/jats:p><jats:p>In ARMC5-mutuated patients with PBMAH, unilateral total adrenalectomy on the\n                        side with more pronounced nodularity appears to be an effective treatment\n                        option. Propranolol may be considered as an alternative or adjunctive\n                        therapy to ULA for managing hypercortisolism in those with ARMC5\n                        mutations.<\/jats:p>","DOI":"10.1055\/a-2559-9643","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T23:46:33Z","timestamp":1747093593000},"page":"235-245","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Propranolol Combined with Different Modalities of\n                    Unilateral Adrenalectomy in a Case Series of 4 ARMC5-mutated\n                    Patients"],"prefix":"10.1055","volume":"133","author":[{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated\n                    Hospital with Nanjing Medical University, Nanjing, China"},{"name":"Department of Endocrinology, Jurong Hospital Affiliated to Jiangsu\n                    University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baowen","family":"Yu","sequence":"additional","affiliation":[{"name":"Nanjing First Hospital, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated\n                    Hospital with Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated\n                    Hospital with Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Qi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated\n                    Hospital with Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1210\/jcem-24-10-947","article-title":"Cushing\u2019s syndrome: Nodular cortical hyperplasia of adrenal glands with clinical\n                    and pathological features suggesting adrenocortical tumor","volume":"24","author":"M A Kirschner","year":"1964","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s12022-022-09710-8","article-title":"Cushing\u2019s syndrome due to bilateral adrenal cortical disease: Bilateral\n                    macronodular adrenal cortical disease and bilateral micronodular adrenal\n                    cortical disease","volume":"33","author":"M Araujo-Castro","year":"2022","journal-title":"Endocr Pathol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"4417","DOI":"10.1210\/jc.2015-2662","article-title":"Unilateral adrenalectomy as a first-line treatment of Cushing\u2019s syndrome in\n                    patients with primary bilateral macronodular adrenal hyperplasia","volume":"100","author":"E Debillon","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1210\/jc.2015-1818","article-title":"Treatment of Cushing\u2019s syndrome: An Endocrine Society Clinical Practice\n                    guideline","volume":"100","author":"L K Nieman","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"E1784","DOI":"10.1210\/jc.2014-1265","article-title":"ARMC5 mutations are common in familial bilateral macronodular adrenal\n                    hyperplasia","volume":"99","author":"L Gagliardi","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1093\/ejendo\/lvad066","article-title":"European Society of Endocrinology clinical practice guidelines on the management\n                    of adrenal incidentalomas, in collaboration with the European Network for the\n                    Study of Adrenal Tumors","volume":"189","author":"M Fassnacht","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/MED.0000000000000061","article-title":"Primary bilateral macronodular adrenal hyperplasia","volume":"21","author":"A De Venanzi","year":"2014","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1210\/endrev\/bnac034","article-title":"Clinical, pathophysiologic, genetic, and therapeutic progress in primary\n                    bilateral macronodular adrenal hyperplasia","volume":"44","author":"J Bertherat","year":"2023","journal-title":"Endocr Rev"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1210\/jc.2002-021362","article-title":"Cushing\u2019s syndrome secondary to adrenocorticotropin-independent macronodular\n                    adrenocortical hyperplasia due to activating mutations of GNAS1 gene","volume":"88","author":"M C Fragoso","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1210\/jc.2009-0516","article-title":"Clinical and genetic heterogeneity, overlap with other tumor syndromes, and\n                    atypical glucocorticoid hormone secretion in adrenocorticotropin-independent\n                    macronodular adrenal hyperplasia compared with other adrenocortical tumors","volume":"94","author":"H P Hsiao","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1530\/EJE-21-1032.","article-title":"Identification of predictive criteria for pathogenic variants of primary\n                    bilateral macronodular adrenal hyperplasia (PBMAH) gene ARMC5 in 352\n                    unselected patients","volume":"187","author":"L Bouys","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s12020-016-0988-4","article-title":"Do patients with incidentally discovered bilateral adrenal nodules represent an\n                    early form of ARMC5-mediated bilateral macronodular hyperplasia?","volume":"53","author":"H Emms","year":"2016","journal-title":"Endocrine"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.1210\/jc.2013-1470","article-title":"Clinical review: Outcome of bilateral adrenalectomy in Cushing\u2019s syndrome: A\n                    systematic 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Long-term follow-up of four cases","volume":"146","author":"C Lamas","year":"2002","journal-title":"Eur J Endocrinol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/1752-1947-6-312","article-title":"Successful treatment for adrenocorticotropic hormone-independent macronodular\n                    adrenal hyperplasia with laparoscopic adrenalectomy: A case series","volume":"6","author":"T Ito","year":"2012","journal-title":"J Med Case Rep"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/cen.12763","article-title":"An analysis of different therapeutic options in patients with Cushing\u2019s syndrome\n                    due to bilateral macronodular adrenal hyperplasia: A single-centre\n                    experience","volume":"82","author":"N M Albiger","year":"2015","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.ecl.2018.01.004","article-title":"Adrenal surgery for Cushing\u2019s syndrome: An update","volume":"47","author":"G Di Dalmazi","year":"2018","journal-title":"Endocrinol Metab Clin North Am"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1055\/a-0998-7884","article-title":"Unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia:\n                    Analysis of 71 cases","volume":"128","author":"M Sheikh-Ahmad","year":"2020","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"17680","DOI":"10.1038\/s41598-022-22676-1","article-title":"Usefulness of cortisol\/ACTH ratio (CAR) for diagnosis of Cushing\u2019s syndrome:\n                    Comparison of CAR with findings in dexamethasone suppression test","volume":"12","author":"Y Iwamoto","year":"2022","journal-title":"Sci Rep"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1056\/NEJM199711133372004","article-title":"Propranolol therapy for ectopic beta-adrenergic receptors in adrenal Cushing\u2019s\n                    syndrome","volume":"337","author":"A Lacroix","year":"1997","journal-title":"N Engl J Med"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"6279","DOI":"10.1210\/jc.2018-02638","article-title":"Mifepristone treatment in four cases of primary bilateral macronodular adrenal\n                    hyperplasia (BMAH)","volume":"104","author":"P Cohan","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e77","DOI":"10.4158\/EP12346.CR","article-title":"Adrenocorticotropic hormone independent macronodular adrenal hyperplasia due to\n                    aberrant receptor expression: Is medical treatment always an option?","volume":"19","author":"O Karapanou","year":"2013","journal-title":"Endocr Pract"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.4158\/EP12346.CR","article-title":"Transient efficacy of octreotide and pasireotide (SOM230) treatment in\n                    GIP-dependent Cushing\u2019s syndrome","volume":"43","author":"V Preumont","year":"2011","journal-title":"Horm Metab Res"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1530\/EJE-10-0195","article-title":"Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: A\n                    frequent finding in a prospective study of 32 patients with overt or subclinical\n                    Cushing\u2019s syndrome","volume":"163","author":"R Lib\u00e9","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1530\/EJE-14-0913","article-title":"Rapid control of severe neoplastic hypercortisolism with metyrapone and\n                    ketoconazole","volume":"172","author":"J B Corcuff","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1530\/EJE-15-0642","article-title":"ARMC5 mutations in a large French-Canadian family with cortisol-secreting\n                        \u03b2-adrenergic\/vasopressin responsive bilateral macronodular adrenal\n                    hyperplasia","volume":"174","author":"I Bourdeau","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e2020GH000268","DOI":"10.1029\/2020GH000268","article-title":"Premature deaths in Brazil associated with long-term exposure to PM2.5 from\n                    Amazon fires between 2016 and 2019","volume":"4","author":"M O Nawaz","year":"2020","journal-title":"Geohealth"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1210\/jcem.85.10.6865","article-title":"Are ectopic or abnormal membrane hormone receptors frequently present in adrenal\n                    Cushing\u2019s syndrome?","volume":"85","author":"H Mircescu","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1056\/NEJM199911183412104","article-title":"Leuprolide acetate therapy in luteinizing hormone--dependent Cushing\u2019s\n                    syndrome","volume":"341","author":"A Lacroix","year":"1999","journal-title":"N Engl J Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/s41574-022-00718-y","article-title":"Primary bilateral macronodular adrenal hyperplasia: Definitely a genetic\n                    disease","volume":"18","author":"I P Cavalcante","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S2213-8587(21)00236-9","article-title":"Loss of KDM1A in GIP-dependent primary bilateral macronodular adrenal\n                    hyperplasia with Cushing\u2019s syndrome: A multicentre, retrospective, cohort\n                    study","volume":"9","author":"F Chasseloup","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.gim.2021.09.018","article-title":"KDM1A inactivation causes hereditary food-dependent Cushing syndrome","volume":"24","author":"A Vaczlavik","year":"2022","journal-title":"Genet Med"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2559-9643.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T23:24:46Z","timestamp":1747783486000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2559-9643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":32,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2025,5,20]]},"published-print":{"date-parts":[[2025,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2559-9643","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"type":"print","value":"0947-7349"},{"type":"electronic","value":"1439-3646"}],"subject":[],"published":{"date-parts":[[2025,5]]}}}